Amperometric biosensors are known in the medical industry for analyzing blood chemistry. Early biosensors, also known as enzyme electrodes, were first proposed by Clark and Lyons and implemented by Updike and Hicks. Enzyme electrodes typically include an oxidase enzyme, such as glucose oxidase, that is immobilized behind a dialysis membrane at the surface of an electrode. In the presence of blood, the membrane selectively passes an analyte of interest, e.g. glucose, to the oxidase enzyme where it undergoes oxidation or reduction, e.g. the reduction of oxygen to hydrogen peroxide. Amperometric biosensors function by producing an electric current when a potential sufficient to sustain the reaction is applied between two electrodes in the presence of the reactants. For example, in the reaction of glucose and glucose oxidase, the hydrogen peroxide reaction product may be subsequently oxidized by electron transfer to an electrode. The resulting flow of electrical current in the electrode is indicative of the concentration of the analyte of interest.
Applications for amperometric biosensors include measuring analytes in blood-borne gases, electrolyte levels in blood and in particular, blood glucose concentration. For measuring glucose, subcutaneous methods have been proposed. For example, see Renard, “Implantable Glucose Sensors for Diabetes Monitoring,” Minim Invasive Ther Allied Technol, Vol. 13, No. 2, pp. 78-86 (2004). While these minimally invasive glucose monitoring systems properly display trends in plasma glucose concentration, they do not track glucose accurately enough to be used for intensive insulin therapy, for example, where inaccuracy at conditions of hypoglycemia could pose a very high risk to the patient. In addition, sensors based upon the enzyme glucose oxidase need to have access to adequate oxygen to provide a linear glucose response. Sensor systems optimized for subcutaneous tissue would not necessarily function well in venous blood, where oxygen tension can be 20 mm Hg or less.
At the present time, the most reliable way to obtain a highly accurate blood glucose measurement in an ICU patient is by a direct time-point method, which involves drawing a blood sample and sending it off for laboratory analysis. This is a time-consuming method that is often incapable of producing needed results in a timely manner. Despite ongoing research in this field, many improvements in glucose monitoring are still needed.
One of the difficulties impeding the development of an intravenous amperometric sensor is that the sensor must be small enough to be suspended within a blood vessel, but robust enough to immobilize an enzyme so that a reaction may be sustained for a sufficient length of time. An intravenous sensor must also be biocompatible, such that it does not release any toxins into a patient, and when implanted, e.g. through a catheter in a femoral vein, discourages clotting of blood at the membrane surface that would prevent plasma from diffusing to the enzyme layer.